PAOLA-1

The double-blind phase 3 PAOLA-1 (NCT02477644) trial randomized 806 patients with advanced ovarian cancer 2:1 to either receive olaparib plus bevacizumab (N=537) or placebo plus bevacizumab (N=269).¹Ray-Coquard et al. N Engl J Med. 2019; doi:10.1056/NEJMoa1911361 Eligible patients had a Federation of Gynecology and Obstetrics (FIGO) stage III or IV high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Patients with other non-mucinous epithelial ovarian cancers were only eligible if they were found to have germline BRCA1 or BRCA2 mutations. The primary efficacy endpoint was the PFS. Patients were stratified according to the tumour BRCA mutational status.

Results

At a median follow-up of 22.9 months, the median PFS was significantly longer for patients receiving maintenance bevacizumab plus olaparib than for patients receiving bevacizumab plus placebo, 22.1 vs 16.6 months, respectively (HR=0.59; 95% CI, 0.49-0.72; p<0.001). Subgroup analysis showed a similar PFS benefit in patients with tumours positive for homologous recombination deficiency (HRD) with BRCA mutations (37.2 months vs 17.1 months) and HRD-positive without BRCA mutations (28.1 months vs 16.6 months), both for the olaparib and placebo groups, respectively.

Safety

Adverse effects were consistent with the established safety profile of olaparib and bevacizumab, with higher percentage fatigue (53% vs 32%), nausea (53% vs 22%) and anaemia (41% vs 10%) in patients receiving olaparib and bevacizumab than placebo and bevacizumab.